title: Neonatal hypercalcemia due to a homozygous mutation in the calcium-sensing receptor: failure of cinacalcet.
abstract: A neonate affected by a novel inactivating mutation in the calcium-sensing receptor (CASR) gene is presented. This mutation is homozygously inherited and has not been previously described. A deletion in exon 5 (c.1392_1404del13) of the gene causes a loss of function of the receptor, which results in neonatal severe hyperparathyroidism and an ensuing extreme hypercalcemia. In a case of homozygosis of the CASR gene, the use of cinacalcet is the second reported calcimimetic treatment attempt and the first treatment attempt prior to surgery. However, because of the type of mutation, parathyroid surgery was necessary at 4 months of age after therapeutic failure. Because there are multiple mutations that affect the CASR gene in different ways, treatment with cinacalcet as an alternative to surgery may be valuable in homozygous cases that are caused by different mutations than the reported case.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Juan Ramón Jiménez Hospital, Huelva, Spain. edusoblechero@hotmail.com
authors.forename: Eduardo
authors.initials: E
authors.lastname: García Soblechero
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Ferrer Castillo
authors.forename: Belén
authors.initials: B
authors.lastname: Jiménez Crespo
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Domínguez Quintero
authors.forename: Concepción
authors.initials: C
authors.lastname: González Fuentes
mesh_terms: D057966:Calcimimetic Agents / Q000627:therapeutic use*; D000069449:Cinacalcet; D004252:DNA Mutational Analysis; D004351:Drug Resistance / Q000235:genetics; D005091:Exons; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D006934:Hypercalcemia / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D049950:Hyperparathyroidism, Primary / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D009281:Naphthalenes / Q000627:therapeutic use*; D010641:Phenotype; D044169:Receptors, Calcium-Sensing / Q000819:agonists* / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D017211:Treatment Failure
chemical_list: C095550:CASR protein, human; D057966:Calcimimetic Agents; D009281:Naphthalenes; D044169:Receptors, Calcium-Sensing; D000069449:Cinacalcet